Vanishing bile duct syndrome associated with pazopanib after progression on pembrolizumab.

Pazopanib, a tyrosine kinase inhibitor, has been a standard first-line treatment for metastatic renal cell carcinoma (mRCC). Recent trials combining pazopanib with programmed cell death protein 1 (PD-1) inhibitors, including pembrolizumab, have shown excessive hepatotoxicity. We report a case of fatal hepatotoxicity from vanishing bile duct syndrome (VBDS) associated with pazopanib treatment, in a patient previously exposed to pembrolizumab. This is the first report of pazopanib-induced VBDS. We postulate whether prior exposure to pembrolizumab predisposed towards pazopanib-induction of VBDS, and discuss potential risks of sequential PD-1 inhibitor followed by pazopanib in mRCC, due to prolonged half-lives of PD-1 inhibitors.